Enhanced delivery of quercetin and doxorubicin using β-cyclodextrin polymer to overcome P-glycoprotein mediated multidrug resistance.

Synthesis of β -CDP/QD NCs using epichlorohydrin linker to overcome. P-glycoprotein (P-gp) mediated MDR in cancer cells. The β -CDP/QD NCs enter the MDR cancer cells through endocytosis. The QCT released from the nanocarrier enhances the intracellular availability of DOX via blocking the drug efflux function of P-gp. [Display omitted] • The β -CDP/QD NCs were successfully synthesized by the freeze-dried method. • Spectroscopic and microscopic studies evaluate the encapsulation of drugs in polymer. • The β -CDP/QD NCs show burst and sustained release of quercetin and doxorubicin. • β -CDP/QD NCs show enhanced apoptotic cell death in MDR cancer cells. In this study, we prepared a β -cyclodextrin polymer (β -CDP) co-loaded quercetin (QCT) and doxorubicin (DOX) nanocarrier (β -CDP/QD NCs) by freeze-dried method to combat P-glycoprotein (P-gp) mediated multidrug resistance (MDR) in KB-ChR 8–5 cancer cells. Various microscopic and spectroscopic techniques were employed to characterize the prepared nanocarrier. The molecular docking studies confirm the effective binding interactions of QCT and DOX with the synthesized β -CD polymer. The in vitro drug release study illustrates the sustainable release of DOX and QCT from the β -CDP nanocarrier. Further, we noticed that the QCT released from the β -CDP nanocarrier improved the intracellular availability of DOX via modulating P-gp drug efflux function in KB-ChR 8–5 cells and MCF-7/DOX cancer cells. Cell uptake results confirmed the successful internalization of DOX in KB-ChR 8–5 cells compared with free DOX. Cell-based assays such as nuclear condensation, alteration in the mitochondrial membrane potential (MMP), and apoptosis morphological changes confirmed the enhanced anticancer effect of β -CDP/QD NCs in the resistant cancer cells. Hence, QCT and DOX co-loaded β -CDP may be considered effective in achieving maximum cell death in the P-gp overexpressing MDR cancer cells. [ABSTRACT FROM AUTHOR]